Update on checking procedures performed by the health authorities on the poly implant prothèse company
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Update on checking procedures performed by the health authorities on the poly implant prothèse company

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Medical devices
18/10/2012

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Informations

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Published 18 October 2012
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Language English
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SITUATION UPDATE ON CHECKING SERUPREDOC

PERFORMED BY THE HEALTH TIEIHTROAUS

ON THE POLY IMPLANT PROTHÈSE COMPANY

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The Minister

Our Ref.: cab/CR/


MINISTRY OF LABOUR, EMPLOYMENT AND HEALTH

Paris, 07 DEC 2011

OBJECT: Overview of all the controls performed on the company Poly Implant Prothese (IPP)

Afssaps found an abnormal increase in the number of premature ruptures observed on implants pre‐
filled with silicone gel manufactured by Poly Implant Prothese (IPP) during the last quarter of 2009.

An inspection of PIP facilities took place from 16 to 18 March 2010: the collected findings showed
that the implants were filled with a different gel from that declared by the company during
marketing and in the manufacturing files.

The conclusions of this inspection lead to the issue of an Afssaps health policy decision on 29 March
2010, which suspended the marketing, ribution,dist export and use of PIP silicone‐gel‐filled breast
implants.

Without anticipating the results of criminal proceedings, please could you send me a complete
overview of the controls conducted by the health authorities on the company Poly Implant Prothese
(PIP) since its creation, as well as measures implemented after these inspections.

The deadline for sending this overview is end January 2012.

Mr. Jean‐Yves GRALL
Director‐General of Health
14 avenue Duquesne 75007 PARIS

Mr. Dominique MARANINCHI
Director‐General of Afssaps
143‐147 Boulevard Anatole France
93285 Saint Denis cedex

127 RUE DE GRENELLE‐75700 PARIS
TELEPHONE: 01 44 38 38 38‐FAX: 01 44 38 20 10

[Signed]

Xavier BERTRAND

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HEALTH
Directorate‐General for Health
The Director‐General

Dear Sir,

Paris 01FEB 2012

AGENCY
The General Director


To

and Health

In your letter of 07 Dec. 2011 you asked us to send a complete overview of the controls performed
by the health authorities on the company Poly Implant Prothese (PIP) and the measures taken after
these inspections.
In order to best illustrate this analysis by factual evidence, the methodology adopted is based on a
chronological analysis from 1995 until today exclusively using documents found in the Ministry
archives and at AFSSAPS.
Please find below all the findings presented in the enclosed report.
This report first provides a review of the regulations and organisation of the administrative
authorities and treatment by cosmetic and reconstructive surgery. This is followed by a detailed
chronological historical analysis, an analysis of device vigilance data, detailed accounts of the
inspections performed by the health authorities, a summary of the currently available toxicology
data on the silicone gels used to fill PIP breast implants, the specific actions implemented by the
health authorities from 2010 and the international repercussions of this dossier.
The main conclusions drawn after this analysis allowed us to make several proposals to prepare the
future and ensure the improved safety of use of these medical devices.
Yours Sincerely

The General Director of Health
[Signed]
Dr Jean‐Yves GRALL

The General Director
[Signed]
Prof. DominiqueMARANINCHI

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Introduction

the production of breast implants.

silicone gel‐prefilled breast implants.

Afssaps.

over the following weeks.

patients with these breast implants.

women ,ocnsulting even in the absence of any clinical signs of a deterioration of the implant.

official documents, or were identified from an archived document.

This report is the subject of the present citauplboi.n

4 / 170


1. REGULATION AND ORGANISATION OF THE ANIMDRTSIVITAE AUTHORITIES AND
CARE MODALITIES IN COSMETIC AND RECONSTRUCTIVE SURGERY 6
1. Regulation of medical devices 6
2. Specific regulations and health policy measures regarding breast implants 7
3. Regulation and organisation of the Medical Device Vigilance system 11
4. Organisation of the isinattreivmda authorities and sites for fitting breast implants 11

II. CHRONOLOGICAL ANALYSIS OF THE AVAILABLE DATA 14
1. From creation PIP society until the the health policy decision of 29 March 2010 14
2. 1995 to 1999 14
3. 1998 to May 2000 17
4. 2000 (June, onward) 18
5. 2001‐2010 (March) 21
2. From the consequences of the marketing suspension of the PIP implants up to 2012 35
1. 2010 (from March) 35
2. YEAR 2011 49
3. YEAR 2012 55

III. MEDICAL DEVICE VIGILANCE 57
1. Period before March 1999 57
2. Period after March 1999 58
3. Minor events act as background noise. 58
1‐ The specific evaluation of reports related to breast implants 58
2‐ Medical Device Vigilance data concngerni the PIP silicone gel breast implants 60
3‐ Vigilance analysis and ectiveretrosp isnoitagitsevn following the DPS 70
4‐ The emergence of new sanitary signals following the report of one case of anaplastic lymphoma of
the breast 82

IV. INSPECTIONS PERFORMED BY THE TSARITEVINIMDA AUTHORITIES 83
1. Inspection of Poly Implant Prothèse conducted in 1996 83
2. Inspections of the Poly Implant Prothèse company conducted in 2001 and 2010 84

V. SUMMARY OF THE AVAILABLE LACITICOXOGOL DATA ON SILICONE GELS USED TO FILL
POLY IMPLANT PROTHESE BREAST IMPLANTS 94
1. Introduction 95
2. cochhysiPcimela and mechanical acarritechasitno of breast implants 96
1. Raw materials 96
2. Mechanical tests and cosihyplacimehc analyses 98
3. Conclusion 101
3. gilolcaoTixoc studies on finished products 102
1. oTixlgicacolo tests in the NUSIL gel conformity assessment documents 102
2. aciglToxicolo tests conducted on PIP gels 106
3. Summary tables of studies conducted with PIP gels 112
4. General conclusion 113
5. References 119

VI. SPECIFIC HEALTH SAFETY ACTIONS TAKEN FROM 2010 121

VII. NATIONALITNRE REPERCUSSIONS OF THE POLY IMPLANT PROSTHESIS BREAST
IMPLANT DOSSIER 132

VIII. MAIN CONCLUSIONS AND PROPOSALS 135

143

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1. admithe ratinistev atulegRd ann ioasinagro fo noit
authorities and care modalities in cosmetic and
reconstructive surgery

1.

Regulation of medical devices

Breast implants are governed by the current law and regulations on medical devices.

implantable medical devices.1

Law no. 94/42 on Public Health and social Welfare2 came into effect on 18 January 1994.

goods.

throughout the European Community market. The latter, alone, may be marketed and installed.

based on a total sinomrahn.ioat

process and the product. This leads to the granting of CE marking.

commission for ificcertntaoi from all European NBs.


1 tum a ob9109nu elegithe ing atch eht fo snoitalsres teta SermbMecaitev agdrni ge SereDiivct90e 583/CEE/ fo J 02
implantable medical devic es.
2 er CEE/5t evitaltiecir D380/ 9vem debaeld vcilativeo aclant impictIs sethbora tponseand no. 93/42/EEC of the Council of
14 June 1993 relative to medical devi ces.
6 / 170

Regarding class IIa, IIb, and III medical devices, the NB evaluates both the technical donoitatnemuc and the
manufacturers quality assurance system. The depth of review by the notified body will depend on the risk
associated with the product under ioatn.nscoerid

For class III devices (such as breast implants since 2003, see below), the design file of the product is
systematically reviewed. The assessment of the whole quality assurance system includes an initial audit at the
manufacturer's premises. Following the assessment of these two aspects, the NB delivers two reitcet,sifac
allowing the afunrutcrmea to declare its product compliant with the essential ntsequiremer of the Directive
and use the EC mark. The afunrutcearm can then market its product in all European countries.

For IIa and IIb‐class devices, only parts of the design file are reviewed.

The dturefucamna and marketed products should comply with the technical documents, in particular with the
design file on which the notified body based and delivered its certificate. Any change to the product in(udclgin
the raw materials) should be declared to the NB by the mtuacufaner,r bfena.drohe Once the EC certificate has
been delivered, on‐site audits are regularly carried out by the NB, general once a year, as long as the product is
on the market. All audits by the NB are described in a report submitted to the rermanufactu by said body.

Therefore, according to European legislation, the NB is sponreesibl for assessing, auditing and certifying the
compliance of the process followed by the rerutcafunam to demonstrate that the essential tsemenquirre of
the European directive are being met. The NB informs the qualified authority (the authority which appointed
the NB) of all delivered, modified, completed, ,edndpessu withdrawn or refused rec.sitifacet The NB should
provide its qualified authority, upon request, with any information relevant to these s.tecafitierc It should be
noted that the European Directive does not require automatic transmission of the assessment files, including
the audit reports that helped with the ointrficitace process.

Therefore, the principles of the New Approach (NA) require the tatiemenimplon of principles of confidence,
competence and tycnerapsnar (in particular toward notified bodies) to guarantee reliable compliance
assessment.

The qualified national authorities (in France: AFSSAPS) have an additional power to intervene once the product
is on the market if information from market surealcnevli or Medical Device Vigilance reports events puts the
compliance of the marketed device in question. For this purpose, AFSSAPS has the following tools: vigilance
monitoring, document checking and laboratory testing of the products as well as inecspnoit.s

Lastly, information concerning class IIa to class III devices should be mcouminacetd to Afssaps when they are
marketed or used.

The Directive was transposed into French law no. 94/43 of 18 January 1994 pertaining to public health and
social welfare.

2. Specific regulations and healg brrdinregares aetsusaem yciop ht
implants

Within the framework of the regulation of medical devices, the health authorities have designed special
measures for breast implants.

a) United States

In the United States, a Marketing itnoAsarihout system was set up by the Food and Drug imdAstnitiraon (FDA)
for breast implants as early as 1976.

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In view of a suspicion of autoimmune disease and observed cases of ruptures and leaks, the American Health
Agency (FDA) ordered a moratorium on silicone gel implants in January 1992 and turned this moratorium into
a prohibition in April 1992. However, the use of such implants was permitted within clinical trials for breast
reconstruction or for the rtelpcamene of ruptured implants. In November 2006, marketing these implants was
again allowed through a "Pre Market Approval" (PMA) supported by clinical studies provided by the
manufacturers. Two manufacturers (ALLERGAN and MENTOR) received a PMA, but PIP silicone gel implants
never received a PMA.

Regarding breast implants prefilled with saline, the American marketing procedure was an equivalence
clearance (510k process) until 2000. Later, the FDA decided to strengthen the conditions for the marketing of
saline‐prefilled breast implants and have them go through a PMA‐type approval. The amunaftcrures who
submitted a PMA request remained authorised to market their implants until the results of the final
assessment.

b) Europe and France

Once a product is EC marked, it can be freely moved across all European markets within the framework of the
"New Approach" on which European directives are based, gniduclin the Directive on medical devices. This has
been the case for breast implants, regardless of the filling product.

It should be noted, however, that France is the only European country that took measures regarding both
silicone gel and hydrogel prefilled breast implants. Later, it played a proactive role to restrict the conditions
under which this type of implant was brought back on the market.

Following the decision made by the U.S. authorities in January 1992 to restrict the use of silicone‐filled breast
implants to clinical trials, the French Ministry of Health decided to impose a moratorium on 24 January 1992
regarding the implantation of silicone gel breast implants until Prof. Gervais had submitted the suoisncnolc of
his report that had been commissioned by the Minister in June 1992.

The moratorium was renewed in October 1992 and a second panel of experts, chaired by Prof. Servant, was
appointed to compile a report for submission to the Minister in March 1993. The moratorium was renewed in
October 1993 but lifted on 29 September 1994.

This was because of the following regulation changes:

Standard AFNOR S 94 350 pertaining to breast implants was published in August 1994.

The ministerial order of 8 August 1994, modified by an order of 14 October 1994, set up a national approval
procedure for devices or products used for prevention, diagnosis or therapy, to be listed in a ministerial order,
and regulated the marketing approval of breast implants.

the neadocmmsitnore of the National Committee for approvals.

1995 was a turning point due to the progressive ntaoimentmplei of the EC legislation and the set‐up of French
health policy measures. Thus, with effect f 1stJanuary 1995, a breast implant could only be sold on the
rom
French market after national approval or the granting of EC marking which became mandatory for all medical
devices after 14 June 1998.

On 24 April 1995, the Minister for Economic Affairs suggested that the Health Minister should issue an order
to suspend the factug,rinmanu importing, marketing, and ioatntlaipmn of silicone gel‐filled breast implants,

8 / 170

based on clause L.221‐5 of the French Consumer Code (Code de la cnoosmmation), consgidienr in particular
the local risks associated with this type of breast implant.

Marketing authorisation for breast implants prefilled with any product other than saline was suspended in
France for a period of time not to exceed twelve months, following the publication of a ministerial order on 10
May 1995.

concerning suspension of the Marketing Authorisation for those breast implants.

authorisation in the country of .nedttasonii

Moreover, the susionpens did not apply to breast implants that:

Health Code.

being at the devellatnempo stage).

been fully evaluated from a technical and clinical t.pointands

4

3

Moreover, the DH wished to check implantable devices that have an aesthetic purpose, other than the breast
implants (in particular liquid silicone for injection). This is why a new ministerial order was suggested to the
ministry; it used the same provisions as the order of 28 May 1997, with a broadened scope on aesthetic
implants with identical issues in terms of structure (calf prostheses and testicular implants) or composition
(liquid silicone for no.)ceitijn



3 volaa ccpArpor pde- sionroviciH uPlb hoCaetl-165.6 Le thf ot gnidroesualc oredew tiih nht erihotisa donivelm laekragnittua
framework of the approval proced ure
4 laid down in the provisions of clause 8.1 of Direc no.tiv24E/9 /3 f41CEo 19e un Jatel r93m ot evid lacideve ices.
9 / 170

The order of 28 May 1998 ndingssuep the Marketing nhtuAsirooita for iemanplblta medical devices for
aesthetic purposes stated that the arciutfu,annmg import, export, storage, marketing at no cost or against
fees, and implantation of breast or other implants for aesthetic purposes when the filling product was
anything other than saline was suspended for one year; the Marketing Atusatihorion for liquid silicone for
injections for aesthetic purposes was also usspended.

exemption cases of clause no. 2.

At Community level, the European Committee published on 1st July 1998 the "Guidelines for conformity
assessment of breast implants according to directive 93/42/EEC relating to medical devices, MEDDEV. 2.5/7‐
Rev1". This document was developed from the strengthened system of reference of June 1997 that was
submitted to the European Committee by the French authorities and from the neitromenodeaf Pr EN 12180
standard draft.

Law no. 98‐535 of 1st July 1998, the provisions of which were enforced with the nomination of the Director‐
General on 9 March 1999, qualified the latter regarding the regulation, and also the n,ioisneptc checking and
vigilance, of a number of health products, iiduclngn medical devices, and transferred health policy powers
concerning all said products previously exercised by the Health Ministry.

implantable medical devices for aesthetic purposes on 26 May 1999.

When Afssaps was created, the denoitnemerofa ministerial order of 28 May 1998 was extended for another
year by a decision of the Director‐General of the Agency on 26 May 1999; the 'Conseil d'État' cancelled his
decision on 6 November 2000, following an appeal by French surgeons, purely for a technicalit.y

Meanwhile, on 31 May 2000, the Director‐General of the Agency made a new decision for a 6‐month period,
while waiting for additional data from the rersnafucautm of breast implants, to the effect that only implants
meeting the essential qureemirtsen could be marketed on a case‐by‐case basis.

In this matter, the isolated position of the French authorities and the gnenignhttser of the essential
requirements within the assessment reference system as well as the itnedenofamero guidelines led to
consideration of yrpgovileerss restoring Marketing ionuAtasiroht for silicone‐filled breast implants from that
date.

Afssaps and a panel of experts developed nosaciticifsep based on, in particular, the 1997 assessment reference
system and the bsequentsu MEDDEV. By the end of 2001, those specistionfica were included in a
communication from the European Committee. Abiding by this new system of reference enabled
manufacturers to show their compliance for a potential return to marketing. The atrnteinlnaio standards for
breast implants were updated ccadiorylgn.
In addition, upon a dual French and British initiative, breast implants were ralcefissdei as Class III, following the
implementation of directive no. 2003/12/EC of the Committee about sifyclasinger breast implants within the
framework of directive no. 93/42/EEC pertaining to medical devices. This tionficaassirecl ensured that the
technical file of breast implants would have to be submitted to the notified body for evaluation in the EC
marking procedure.

Therefore, saline‐filled implants were not affected by the same measures as silicone or hydrogel implants, and
they were marketed throughout this whole period in France as well as in other European countries.

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